PXD059591-1

PXD059591 is an original dataset announced via ProteomeXchange.

Title	OMIC analyses identified senescence activation in osteogenesis imperfecta osteoblasts that is rescued by 4-PBA treatment
Description	Mutations in collagen I account for the most frequent cause of the skeletal disease osteogenesis imperfecta (OI) and are responsible for delay in protein folding and synthesis of molecules with abnormal structure. A fraction of aberrant collagen molecules is secreted in the extracellular matrix (ECM) where they impair the bone quality, while others are intracellularly retained in the endoplasmic reticulum where they perturb osteoblast homeostasis. The chemical chaperone 4-phenylbutyrate (4-PBA) improves OI osteoblast activity ameliorating ECM composition. To evaluate the consequences of intracellular malfunctioning in OI and to elucidate the mechanism responsible for the described positive effect of 4-PBA in OI, omics techniques were applied to analyze osteoblasts secretome and transcriptome in two well characterized murine models of dominant OI, the Col1a1+/G349C and the Col1a2+/G610C mice. Analyses of the cell culture media by nano LC-ESI-MS/MS and bioinformatic tools identified several senescence associated secretory proteins together with changes in cytoskeletal and cell adhesion proteins. Bioinformatic analyses of transcriptomic data revealed p53 as hub gene supporting a premature senescence activation in both models. Increased senescence-associated β-galactosidase activity, as well as increased gene expression of the cyclin-dependent kinase-inhibitor p16, and a decreased expression of Ki67, indicating a permanent exit from the cell cycle in both mutants confirmed the ainduction of cellular senescence. Senescence proteins were undetectable in secretome collected following 4-PBA incubation that also modified the cytoskeletal and adhesion protein expression. Furthermore, the drug normalized the senescence markers expression and the number of senescent cells. Our study identified senescence as OI osteoblasts hallmark and discover a new positive contribution of 4-PBA to osteoblasts homeostasis.
HostingRepository	PRIDE
AnnounceDate	2026-04-13
AnnouncementXML	Submission_2026-04-12_18:54:47.039.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simona Nonnis
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-09 06:40:34	ID requested
⏵ 1	2026-04-12 18:54:48	announced

10.1111/jcmm.71120;

Besio R, Maffioli E, Palladino E, Sala A, Garibaldi N, Izzi V, Forlino A, Tedeschi G, OMICS Profiling Identifies Signatures of Senescence in Osteogenesis Imperfecta Osteoblasts Counteracted by 4-PBA. J Cell Mol Med, 30(7):e71120(2026) [pubmed]

submitter keyword: proteomics, nanoLC-MS/MS

Elisa Maffioli
contact affiliation	DIVAS, University of Milan
contact email	elisa.maffioli@unimi.it
lab head
Simona Nonnis
contact affiliation	University of Milan
contact email	simona.nonnis@unimi.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059591
     1. Label: PRIDE project
     2. Name: OMIC analyses identified senescence activation in osteogenesis imperfecta osteoblasts that is rescued by 4-PBA treatment